Myocardial infarctions (MI), the leading cause of mortality in industrialized countries, almost exclusively result from the rupture of small, thin walled, lipid filled plaques. When these plaques rupture, they release thrombogenic material into the blood, which leads to clot formation and subsequent vessel occlusion. Until the recent commercial availability of optical coherence tomography (OCT), these small thin walled plaques were beyond the resolution limits of clinical imaging modalities. But while OCT is very sensitive for identifying small thin walled plaques, it's ability to subclassifying them into lipid (unstable versus non-lipid (stable) is poor. Since coronary interventions carry significant risk, determination of a lipid core is essential in risk stratifying for interventional therapy. In this proposal, we use a novel detection scheme utilizing photon pairs (termed biphoton wavepacket or 2nd order correlations {SOC}) with advantageous quantum properties to differentiate lipid from non-lipid plaques. Though typically filtered out as noise with OCT, these biphotons can be measured with OCT system modifications and also allow OCT images to be obtained. Many of the SOC quantum principles utilized in this proposal were originally studied, over the last several decades, using special quantum sources which generate entangled photon pairs approximately one biphoton at a time. These principles have recently been utilized with conventional thermal light. In a paper published in 2008, using a modified OCT set- up, we were able to use thermally generated SOC to differentiate lipid from nonlipid utilizing the quantum phenomena of nonlocality and superposition (spread of the position probability amplitude). However, the set- up required pre-knowledge of the separation between two reflectors that was of limited clinical value, in addition to requiring signal chirping and analysis of offline plots. hat has been overcome with a redesign of the interferometer (only one reflection needed), for which we will demonstrate pilot data from a prototype system. The proposed system needs only a single reflector and one interferometer, with a real time detection scheme (data represented as correlation and anti-correlation peaks). The hypothesis of this proposal is that lipid and non-lipi plaque can be differentiated by analyzing SOC alterations backreflected from plaque. It will be tested by building a clinically viable combined OCT/SOC system and evaluating it with phantoms and in vitro plaque. This is a high impact proposal because 1. The significance is high as it provides a solution for prevention of many MI, representing a substantial mortality and morbidity benefit. 2. It is highly innovative both because it uses thermal quantum SOC at high intensity for identifying the plaque and because an imaging embodiment is developed with no parallel. 3. The team has considerable expertise in OCT, quantum mechanics, basic research, clinical research, and cardiology. 4. The approach develops two novel OCT/SOC embodiments: evaluating their various system parameters on phantoms and atherosclerotic plaque. 5. The environment is structured to produce forefront science from physics and engineering to clinical trials. PUBLIC HEALTH RELEVANCE: Heart attacks, the leading cause of mortality in industrialized countries, almost exclusively result from the rupture of small, thin walled, lipid filled plaques. new technology OCT is very sensitive for identifying small thin walled plaques, but it's ability to subclassifying them into lipid (unstable) versus non-lipid (stable) is poor. We use a novel OCT and quantum mechanics approach to differentiate stable and unstable coronary plaque.